DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .1
Status of the Claims
Claims 12-20 are pending in this application. Claims 12-13 and 15-20 are under examination. Claim 14 is withdrawn.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 02/13/2026 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Response to Arguments
Applicant’s arguments, filed Dec 1 2025, with respect to the rejection of Claim(s) 12, 13 and 15-20 under 35 U.S.C. 103 as being unpatentable over Shiotani et al., U.S. Patent No. 8,927,504, in view of Singh, U.S. Patent Publication No. 2012/0289588, and Honka et al. J Clin Endocrinol Metab, May 2015, 100(5):2015–2023, have been fully considered. While the claims have been amended to limit claims 12 to particular compounds as spelled out below (eriodictyol, β-myrcene, acid, diosmin, luteolin, menthol, sucralose, mannitol, saccharin), the presently pending have been similarly rejected under the same references as detailed below.
Claim Interpretation
Claim 12 is directed to an aspect of ameliorating a pancreas disease caused by fatty pancreas comprising administering an effective amount of a composition as defined therein. The composition is selected from the group of compounds (sweeteners, such as sorbitol, mannitol and/or sucralose), a compound that causes the above compounds (i.e. the sweeteners) to exist in body after administration, and any combinations thereof. Note while the composition is said to be members of the Markush group recited, the method of treating the subject in need thereof comprises administration of an effective amount of a composition. Accordingly, art that teaches the administration of not only the composition consisting the Markush group of compounds but also administration of other drugs or therapeutic agents.
With regard to the treatment of the claimed subject of claims 12 and 20, Applicant’s specification suggests that often times pancreatic fat content and fatty-related pancreatic disorders stem from obesity, which can cause other disease conditions such as diabetes and lower insulin production:
“The pancreas is an organ having both exocrine and endocrine functions in the human body. The exocrine portion includes acini, which secrete a variety of digestive enzymes. The endocrine portion includes pancreatic islets, which secrete hormones, such as insulin, etc., and have a very important effect in maintaining the level of blood glucose. The accumulation of fat in the pancreas may affect the functions of the pancreas and further cause a pancreas disease, diabetes mellitus, or other related disorders. In particular, diabetes mellitus is a disease caused by abnormal glucose metabolism. There are two types of diabetes mellitus, including non-insulin dependent or adult type, also known as diabetes mellitus type II; and insulin dependent or infant type, also known as diabetes mellitus type I. In general, diabetes mellitus type II usually occurs in adults, is highly associated with obesity, and can be controlled by appropriate exercise, diet and medications; while patients suffering from diabetes mellitus type I are mostly children and adolescents, who cannot produce enough insulin inside the body and must be administered insulin by injection to maintain life.”
See paragraph 0003, of Applicant’s Specification (emphasis added).
Claim Objections
Claim 20 is objected to because of the following informalities:
The claimed method to treat a subject suffering from fatty pancreases and conditions associated with it, comprises the administration of
an effective amount of a composition as an active ingredient to the subject, wherein the composition is selected from a group of compounds consisting of eriodictyol, β-myrcene, diosmin, luteolin, menthol, sucralose, mannitol, and saccharin, a compound that causes any of the above compounds to exist in body after administration, and any combinations thereof . . . .
The claim is objected to as it recites members of the Markush group consisting of the various sweeteners, it recites the term “and” between saccharin and sucralose, e.g., “saccharin, and sucralose.” If the Markush group is intended to only include as members of the Markush group those group of sweeteners, with the last member of the group of the Markush is supposed to be “sucralose,” then this objection will be withdrawn by the Examiner.
However, if the Markush group is intended to also include a compound that cause any of the above [sweetener] compounds to exist in body after administration and have the last member of the Markush group be “any combinations thereof,” then the “and” between “saccharin,” and “sucralose” must be deleted.
Appropriate correction is required.
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
This application currently names joint inventors. In considering patentability of the claims under 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicants are advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103(a).
Claims 12, 13 and 15-20 are rejected under 35 U.S.C. 103 as being unpatentable over Shiotani et al., U.S. Patent No. 8,927,504, issued January 6, 2015, in view of Singh, U.S. Patent Publication No. 2012/0289588, published on November 15, 2012 and Honka et al. J Clin Endocrinol Metab, May 2015, 100(5):2015–2023. Shiotani ‘504 patent Singh US ‘588 and Honka were cited in the previous office actions.
Applicant’s invention is generally directed to a method for reducing pancreatic fat content and/or treating fatty-related pancreatic disorders via the administration of composition comprising certain compounds that include specific sweeteners (e.g. sucralose, mannitol and sorbitol)2, celluloses and flavoring agents.
Claims 12 and 20 are directed towards a method for:
reducing a pancreatic fat content (intended outcome for the patient),
treating fatty pancreas, or
ameliorating a pancreas disease caused by fatty pancreas,
or regulating pancreatic dysfunction due to fat accumulation
in a subject in need thereof, comprising:
administering an “effective amount” of a composition as an active ingredient to the subject, wherein the composition is selected from a Markush group of compounds consisting of one of several compounds, including the compound claimed sucralose, mannitol and sorbitol (as per claim 12) or mannitol and sucralose (as per claim 20).
and analyzing blood glucose, fasting insulin concentration, or insulin resistance by blood glucose levels, glycated hemoglobin (HbA1C), glucose tolerance test (GTT), blood insulin concentration, homeostasis model assessment of insulin resistance (HOMA-IR).
Similar to claim 12, claim 20 discloses eriodictyol, menthol, mannitol, saccharin, and sucralose.
Claims 12 and 20 read on methods of treating obese patients with type II diabetes (patients in need of “reducing a pancreatic fat content and/or ameliorating a pancreas disease caused by fatty pancreas”). See above, claim interpretation section, where fatty pancreas has a direct link to type II diabetes mellitus, per the specification paragraph 0003.
Regarding claims 12 and 20, Shiotani ‘504 patent teaches therapeutics, comprising the sucralose, mannitol and sorbitol (sweeteners with GLP-1 secretion-stimulating action as claimed), that exhibit superior anti-obesity effects or body weight-reducing (losing) effects and/or body fat mass-reducing effects, see abstract. Shiotani ‘504 teaches the combination of a dipeptidyl peptidase 4 inhibitor and a sweetener having a GLP-1 secretion-stimulating action (i.e., sucralose, mannitol and sorbitol).
Shiotani ‘504 patent teaches that impacts of obesity on diabetes type II on fat cells and the pancreas, and that sucralose stimulates GLP-1 receptors, and acts on the pancreas:
“Examples of causative factors of type 2 diabetes include impaired pancreatic insulin secretion and insulin resistance. Hypertrophy of fat tissue in obesity not only decreases the number of insulin receptors of fat cells, but also accelerates the secretion of insulin resistance-inducing cytokines such as TNF-alpha from fat cells, thereby causing insulin resistance.”
See Shiotani ‘504 patent, paragraph 0008; and:
“GLP-1 (glucagon-like peptide 1) is a peptide hormone that mainly has the augmented action in glucose-stimulated insulin secretion, is primarily secreted from the lower small intestine after meals, and acts in the pancreas. DPP4 deactivates this GLP-1 by hydrolyzing it, as well as DPP4 causes the production of peptides that act as antagonists of GLP-1 receptors.”
See Shiotani ‘504 patent, paragraph 0011.
Regarding claims 12 and 20, also column 13, lines 21-23, where Shiotani ‘504 patent discloses the claimed sucralose, mannitol and sorbitol (sweeteners with GLP-1 secretion-stimulating action). See Figure 1, where a sweetener, equivalent to sucralose, mannitol and sorbitol (see column 13, lines 12-29), fructooligosaccharide demonstrated plasma active GLP-1 activity.
With regard to the compound that causes any of the sweetener compounds to exist in body after administration, Shiotani ‘504 patent discloses various inert carriers (to form a composition), such as binders (gum Arabic, gelatin, sorbit, PVP), excipients (lactose, saccharose, or cornstarch), distilled water, etc., which as pharmaceutical excipients, meet the limitation as claimed. See column 13, line 61 to column 14, line 9).
Regarding the limitations of analyzing blood glucose, fasting insulin concentration or insulin resistance by blood glucose, Shiotani ‘504 patent notes that GLP-1 peptide hormone is known to have an augmented action in glucose-stimulated insulin secretion, see column 1, lines 55-57. A person having ordinary skill in the art (PHOSITA) would have a rationale to look towards analyzing blood glucose, fasting insulin concentration or insulin resistance, as Shiotani ‘504 patent teaches compounds that inhibit enzyme activity of DPP4 inhibitors enhance glucose-stimulated insulin secretion by enhancing the action of intrinsic GLP-1 by means of this inhibitory action, thereby demonstrating blood sugar lowering action, while improving impaired glucose tolerance (i.e., insulin resistance), see column 1, lines 62-68. Shiotani ‘504 patent also notes the role of insulin resistance with regard to obesity and related conditions such as diabetes, hyperinsulinemia, dyslipidemia, hyperlipidemia, arteriosclerosis and heart disease, see column 1, lines 34-41.
Although Shiotani teaches in three specific examples that a pharmaceutical combination comprising a sweetener (sucralose as well as mannitol and sorbitol) acts as an antagonist of GLP-1 receptors and thereby reduces body weight in animal studies (Examples 3, 6 and 7) and provides a reason to analyze blood glucose/fasting insulin concentration or insulin resistance, he does not explicitly teach that the reduction in body weight corresponds to pancreatic fat reduction.
However, a PHOSITA would reasonably expect the fat reduction approach of Shiotani ‘504 patent to result in the reduction of pancreatic fat because it was known in the art that pancreatic fat and obesity scale together. For example, see Singh US Pub ‘588 where he teaches:
“Obesity is a well-documented risk factor for worse outcomes in acute pancreatitis…, including the risk of local complications …, systemic complications such as the systemic inflammatory response syndrome (SIRS), multisystem organ failure (MSOF) and mortality… and the risk of local complications. The sites of visceral fat deposition include the mesentery, omentum, liver…., the pancreas, and the peripancreatic space… It has been suggested that visceral adipose tissue, as measured by waist-to-hip ratio and waist circumference above ideal cut-off value, may be a greater risk factor for worse outcomes in acute pancreatitis than total body fat… Increased fat accumulation in the pancreas and peripancreatic space has been noted in association with increased body weight...”
“Intrapancreatic fat has been shown to increase with BMI in studies evaluating autopsy samples…. The distribution of fat is fairly uniform in the dorsal pancreas and is reduced in the ventral pancreas … Uneven fatty replacement in the pancreas is infrequent (3.2%), and the pattern of fat distribution is not influenced by obesity…” See Singh US Pub ‘588, paragraphs 0004 and 0005 (emphasis added).
Additionally, Honka discloses the objective of this study (27 morbidly obese subjects and 15 healthy control subjects, see page 2016, column 2 Subjects and Methods) was to investigate the effects of weight loss (via bariatric surgery) on pancreatic lipid metabolism and glycemic control, see abstract, Objective and pages 2015-2016. Honka discloses pancreatic fat and fat-free volume, fatty acid uptake, and blood flow were measured as well as parameters of β-cell function, glucose tolerance, and insulin sensitivity, see abstract, Main Outcome Measures; and page 2017, columns 1-2. Honka discloses that its analysis led to the conclusion that weight loss in their obese patients (bariatric surgery) led to not only prominent weight loss accompanied by improvement in glucose homeostasis as per the invention’s claimed methods of analyzing blood glucose and insulin sensitivity (starting at Results section on page 2018, as well as Table 1), but also control of hyperlipidemia and other blood fat indicators, as well as decreases in pancreatic fat deposits, see abstract. Honka provides specific data (see Figure 2 and starting at page 2019), to demonstrate methods of weight loss resulted in reductions of pancreatic fat percentage and pancreatic fat volume, see page 2019, second column. Honka notes the decrease in pancreatic fat volume (that accompanied the total body weight loss and reductions of plasma/blood fat indicators) reflected the reduction in total pancreatic volume 6 months after the procedure, whereas NO change was seen in the fat-free volume of the pancreas, Id.
Additionally, as per the limitation of analysis of claims 12 and 20, Honka discloses that methods of analyzing blood glucose, insulin and insulin sensitivity are known and taught with regard to reductions in obesity and also reductions to fatty pancreas, see Table 1.
Prior to the filing of the present patent application, a PHOSITA following the teachings of the Shiotani would have been prima facie obvious to treat fatty pancreas based on the teachings of Singh and Honka that reduced body fat correlates with reduced pancreatic fat, per MPEP 2143 (combining prior art elements of reduced body fat correlating with reduced pancreatic fat (Singh and Honka) to treat fatty pancreas as per Shiotani, a known method).
Regarding claims 12, 13 and 17 and the limitation of a composition comprising sucralose, claim 1 of the Shiotani ‘504 patent discloses sucralose as claimed by Applicant. Further regarding claim 13 with the limitations of mannitol, Shiotani 504 discloses mannitol as well as sucralose at column 13, lines 20-22.
Regarding claim 15 (simultaneous administration of compounds of the composition) and claim 18 (sequential administration), as Applicant has merely elected a single compound species (sucralose), the Shiotani ‘504 patent discloses that sucralose is administered with another compound for simultaneous, separate or continuous treatment. See column 4, lines 1-4.
Regarding claim 16 and the limitation of fatty pancreas disease, as noted above, the combination of Singh US ‘588 and the Shiotani ‘504 patent disclose treatment of fatty pancreas, see above rejection of claim 12.
Claim 18 limits the method of claim 12 to sequential administration of the claimed compounds. Despite the fact that claim 12 only claims “a composition” is administered to the subject in need, for purposes of art rejection, claim 18 is interpreted as meaning multiple compositions are administered sequentially, rather than the multiple compounds in a single composition consisting of said compounds, as claim 12 currently claims. A PHOSITA administering multiple compositions would routinely optimize the sequential administration of them, as there are limited options for administration of multiple compositions, either simultaneously or sequentially, one after another.
Regarding claim 19 and the limitation of nonalcoholic fatty pancreas disease, as noted above, the combination of Singh US ‘588 and Shiotani ‘504 patent disclose treatment of fatty pancreas (known to be caused by obesity), see above rejection of claim 12. As there are two types of fatty pancreas disease (alcoholic and nonalcoholic), one of ordinary skill in the art would have a rationale to treat either type of fatty pancreas with the claimed method as noted by the cited prior art.
RESPONSE TO ATTORNEY ARGUMENTS:
The Attorney response argues I. The Present Invention Achieves Selective Reduction of Pancreatic Fat, Supported by Experimental Results That Align with the Claimed Scope. To support this statement, the Attorney response states organ-specific fat accumulation/dysfunction is not treated by weight/lipid lowering agents (later referencing US Patent 10925854 statins with their side effects and paradoxical worsening of hepatic steatosis), The Attorney response references Shiotani and its general body-fat-reducing effect via DPP-4 inhibitor/GLP-1 secretion stimulation with sucralose, which it categorizes as fundamentally distinct from the claimed invention. The Attorney response states Shiotani does not teach pancreatic fat reduction (no presentation of mechanism or experimental data to target pancreatic fat via the general body-fat reducing effect).
The Attorney response states mannitol and its combinations of certain compounds (within the scope of the claims), selectively reduce pancreatic triglycerides with no effect on plasma triglycerides or systemic body fat (referencing Tables 1 and 3 and confirmed by Table 2-2’s improvements in pancreatic function and reductions in fat-related pancreatic dysfunction). The Attorney response contrasts the pancreatic targeted claimed invention with conventional lipid/general fat, lowering/reducing strategies (Hsieh, Attached Reference 1) where Hu-610 (comprising mannitol and sucralose) targets pancreatic tissue triglyceride levels in a high fat animal model.
In response to Attorney’s Point I., while the Attorney response argues that its method relies upon reduction of pancreatic fat, treatment of fatty pancreas or improvement of pancreatic disease not taught by the weight loss mechanism of the cited prior art, “the prior art’s mere disclosure of more than one alternative does not constitute a teaching away from any of these alternatives because such disclosure does not criticize, discredit, or otherwise discourage the solution claimed….” In re Fulton, 391 F.3d 1195, 1201, 73 USPQ2d 1141, 1146 (Fed. Cir. 2004).
The claim is directed to treatment of a subject in need (ameliorating a pancreas disease caused by fatty pancreas). As detailed above, such a subject in need includes type 2 diabetes mellitus patients, where such patient is treated in the cited prior art as described above.
Further, in order to overcome the established prima facie case of obviousness, "objective evidence of nonobviousness must be commensurate in scope with the claims [emphasis added] which the evidence is offered to support."3
While the Attorney response the various mechanisms of Table 1, 3 and 2-2, not taught, i.e. unexpected, over the cited prior art, it is pointed out that the methods of claim 12 and 20 do not recite limitations reflecting the specific measure data of Tables 1, 3 and 2-2.
Further, the Attorney response argues that a particular composition, Hu-610 with mannitol and sucralose as individual components, exhibits certain pancreatic targeting activity. However, it is noted that the scope of claims 12 and 20 are far broader than the being limited in scope to mannitol and sucralose and the specific amounts and doses disclosed in said tables.
The Attorney response states that II. Distinct Mechanism for Pancreatic Fat Reduction Independent of Weight Loss (unlike the cited art not a caloric-restriction-based pathway relied upon by sweeteners or GLP-1 related agents predictive of selective reduction of pancreatic fat without weight loss by HU-610 , Ref. 1 Hsieh ). The Attorney response states in 3 bullet points, the cited prior art does not disclose or suggest treatment of (per the claimed invention, mannitol based compositions organ/pancreas specific targeting) fatty pancreas or pancreatic dysfunction arising from fat Accumulation; Modulation of pancreatic physiology impaired by lipid deposition; or Selective reduction of visceral organ fat without systemic fat reduction.
In response to Attorney’s Point II., as detailed above, while the response argues a lack of teaching of the reduction of pancreatic fat is not necessarily taught by cited prior art, as per In re Fulton, alternative disclosures that do not criticize, discredit or discourage the solution claimed does not constitute a teaching away. The prima facie case renders the claimed invention obvious as detailed above by the teachings of Shiotani, Singh and Honka.
Further, in order to overcome the established prima facie case of obviousness, "objective evidence of nonobviousness must be commensurate in scope with the claims [emphasis added] which the evidence is offered to support."4
While the Attorney response argues Tables 1, 2-2 and 3 note the particular mannitol activity with regard to pancreatic fat, as discussed above, the scope of the claimed invention is far broader than just mannitol alone.
The Attorney response states that III. Unpredictable Reduction of Pancreatic Fat Without Body Weight Loss. The Attorney response restates that losing body weight, improving glycemic control or improving physical fitness does not necessarily reduce visceral/pancreatic fat, citing to references 2 (Astrup2009) and 3 (Drucker 2008) directed to GLP-1 analogues. The Attorney response states that general weight loss from fat mass is unevenly distributed across different fat depots (i.e., GLP-1 analogues reducing epicardial fat for example, see Attached References 4 (Jendle 2009) & 5 (Moriano 2015) & 7 (Ishii 2019)) & 8 (Jacobellis); citing to liraglutide reducing hepatic steatosis in NASH Reference 6 (Armstrong 2019); where accordingly, a PHOSITA would not infer from general body-fat reduction-whether induced by sweeteners, GLP-1 analogues, or surgical interventions-that any given compound would selectively reduce pancreatic fat, let alone do so independently of body weight loss. In summary, the Attorney response argues that the prior art cited fails to teach or suggest, (demonstrated by its experimental evidence) selective pancreatic fat reduction; that is independent of body weight loss and targeted improvement of pancreatic dysfunction due to fat accumulation, i.e. a significant and unexpected advance over the cited prior art.
In response to Attorney’s Point III and conclusory remarks., as detailed above, while the intended result of reducing pancreatic fat by the claimed method is argued to be unexpected, if that were the case, in order to overcome the established prima facie case of obviousness, "objective evidence of nonobviousness must be commensurate in scope with the claims [emphasis added] which the evidence is offered to support. As detailed above, the claims do not limit themselves to the evidenced noted by the specification as argued above, and are far broader than the composition Hu-610 (mannitol and sucralose) referred to, and broader than Tables 1, 2-2 and 3, directed to mannitol and its effects on pancreatic fat.
Conclusion and Correspondence
In summary, no claims are allowed. Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to WILLIAM LEE whose telephone number is (571)270-3876. The examiner can normally be reached M-F.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Adam C. Milligan can be reached at (571) 270-7674. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/WILLIAM Y LEE/Examiner, Art Unit 1623
/ADAM C MILLIGAN/Supervisory Patent Examiner, Art Unit 1623
1 This application is a 371 of PCT/CN2016/106607, file date 11/21/2016, where PCT/CN2016/106607 claims priority to US Provisional 62/257,707 11/19/2015.
2 More specifically, Claim 12 has been amended to specifically recite it is directed to the following only: eriodictyol, β-myrcene, acid, diosmin, luteolin, menthol, sucralose, mannitol, and saccharin.
3 MPEP 716.02(d) Unexpected Results Commensurate in Scope With Claimed Invention [R-08.2012]
Whether the unexpected results are the result of unexpectedly improved results or a property not taught by the prior art, the "objective evidence of nonobviousness must be commensurate in scope with the claims which the evidence is offered to support." In other words, the showing of unexpected results must be reviewed to see if the results occur over the entire claimed range. In re Clemens, 622 F.2d 1029, 1036, 206 USPQ 289, 296 (CCPA 1980)
4 MPEP 716.02(d) Unexpected Results Commensurate in Scope With Claimed Invention [R-08.2012]
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